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首页> 外文期刊>Arthritis and Rheumatism >A Critical Role of the Transcription Factor Fli-1 in Murine Lupus Development by Regulation of Interleukin-6 Expression
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A Critical Role of the Transcription Factor Fli-1 in Murine Lupus Development by Regulation of Interleukin-6 Expression

机译：转录因子Fli-1在白细胞介素-6表达调节中鼠狼发育的关键作用

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Objective. The Fli-1 transcription factor is implicated in the pathogenesis of systemic lupus erythema-tosus (SLE), both in humans and in animal models. Dysregulation of interleukin-6 (IL-6) is also associated with SLE. The purpose of this study was to investigate whether Fli-1 directly regulates the expression of IL-6. Methods. Sera were collected from wild-type and Fli-1-heterozygous (Fli-l+/~) MRL/lpr mice, and the concentration of IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6 in the kidney was measured by real-time polymerase chain reaction analysis. T cells were isolated from wild-type and Fli-l+/~ MRL/lpr mice and stimulated with CD3/CD28 beads, and the concentration of IL-6 in the supernatants was measured by ELISA. MSI endothelial cells were transfected with Fli-1 and control small interfering RNA, and the production of IL-6 was compared after lipopolysaccharide stimulation. A chromatin immunoprecipitation (ChIP) assay was performed to determine whether Fli-1 binds to the IL-6 promoter region. Transient transfections with the NIH3T3 cell line were performed to examine whether Fli-1 regulates the expression of IL-6. Results. Fli-l+/~ MRL/lpr mice had significantly decreased IL-6 levels in sera and reduced expression of IL-6 in kidneys as compared to their wild-type litter-mates. T cells isolated from Fli-l+/~ MRL/lpr mice produced less IL-6 than did those from wild-type mice. Inhibiting the expression of Fli-1 in endothelial cells resulted in reduced production of IL-6. The ChIP assay revealed direct binding of Fli-1 to 3 regions within the IL-6 promoter. Fli-1 activated transcription from the IL-6 promoter in a dose-dependent manner. Conclusion. The direct regulation of IL-6 expression by Fli-1 represents one possible mechanism for the protective effect of decreased Fli-1 expression in lupus.
机译：客观的。 FLI-1转录因子涉及在人类和动物模型中的全身狼疮红斑狼疮（SLE）的发病机制。白细胞介素-6（IL-6）的失调也与SLE相关。本研究的目的是研究FLI-1是否直接调节IL-6的表达。方法。从野生型和FLI-1-杂合（FLI-L + /〜）MRL / LPR小鼠收集血清，通过酶联免疫吸附测定法（ELISA）测量IL-6的浓度。通过实时聚合酶链反应分析测量肾脏中IL-6的表达。从野生型和Fli-L + /〜MRL / LPR小鼠中分离T细胞并用CD3 / CD28珠子刺激，通过ELISA测量上清液中IL-6的浓度。用FLI-1转染MSI内皮细胞，并控制小干扰RNA，并在脂多糖刺激后比较IL-6的产生。进行染色质免疫沉淀（芯片）测定以确定FLI-1是否与IL-6启动子区结合。进行瞬时转染与NIH3T3细胞系进行检查，以检查FLI-1是否调节IL-6的表达。结果。与野生型垃圾配合相比，FLI-L + /〜MRL / LPR小鼠在血清中显着降低了血清中的IL-6水平，并减少了肾脏中IL-6的表达。来自Fli-L + /〜MRL / LPR小鼠分离的T细胞产生的IL-6比来自野生型小鼠的小鼠少。抑制内皮细胞中FLI-1的表达导致IL-6的产生降低。芯片测定揭示了IL-6启动子内FLI-1至3个区域的直接结合。 FLI-1以剂量依赖性方式从IL-6启动子激活转录。结论。 FLI-1的IL-6表达的直接调节代表了狼疮中减少的FLI-1表达的保护作用的一种可能机制。

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